The Underestimated Role of Environmental Factors in the Prevention of Invasive Fungal Disease: Experience From a European Childhood Cancer Centre

BACKGROUND: Immunocompromised children with hematologic malignancies or undergoing allogeneic haematopoietic stem cell transplantation (HSCT) are at high risk for invasive fungal diseases (IFDs). Reported incidence varies considerably due to heterogeneous diagnostic criteria, antifungal strategies and environmental conditions. Environmental preventive measures, although highly relevant, remain underrecognised determinants of IFD incidence. METHODS: This retrospective, single-centre trial included paediatric cancer or transplant patients at high risk for IFD treated before (Cohort 1) and after (Cohort 2) relocation of a paediatric cancer centre from a 1990s building to a state-of-the-art facility with improved environmental protection standards (observation periods: 56 and 12 months, respectively). Antifungal prophylaxis continuously followed local standards. IFD was diagnosed according to 2019 EORTC/MSGERC criteria. Primary endpoint was IFD incidence; secondary endpoints included prophylaxis use, IFD management and mortality. RESULTS: This study included 186 patients (Cohort 1: n = 140; Cohort 2: n = 46). Baseline characteristics were comparable between both cohorts. Adherence to prophylaxis standards exceeded 98%, with liposomal amphotericin B being the most common agent. In Cohort 1, 25 possible, probable, or proven IFD occurred, mainly pulmonary aspergillosis, whereas no cases were observed following implementation of environmental measures in Cohort 2 (17.9% vs. 0%, p = 0.002). Most IFD cases occurred in HSCT recipients. IFD was associated with increased mortality (p < 0.0001). CONCLUSIONS: In this contemporary paediatric cancer and transplant setting, environmental protective measures were associated with a marked reduction in IFD incidence, complementing consistent pharmacologic prophylaxis. These findings underscore environmental protection as essential for IFD prevention in high-risk paediatric populations.